Tamás Illés

Decreased bone mineral density in neurofibromatosis-1 patients with spinal deformities.

Abstract: A cross-sectional study was carried out to obtain data on the bone mineral density status of a group of neurofibromatosis-1 patients with spinal deformities, and to search for possible accompanying changes in the bone mineral turnover. Neurofibromatosis-1 is a heredofamiliar disorder that is associated with a variety of skeletal anomalies (mostly spinal deformities) in 10–50% of patients. Intraoperatively, a poor vertebral bone quality has been observed. Efforts have been made to identify factors preventing curve progression, to optimize operational planning and to explain the pathomechanism. As part of the preoperative evaluation, dual-energy X-ray absorptiometry was used to assess the bone mineral density of the lumbar spine in 12 patients with neurofibromatosis-1, supplemented by laboratory blood/urine investigations. A significant decrease in bone mineral density of the lumbar spine was measured. An inverse relation was suggested between the severity of scoliosis and the lumbar spine Z-scores. No pivotal alterations were identified in the laboratory measurements. The bony tissue abnormality observed intraoperatively in neurofibromatosis-1 patients may be described as a diminution of the axial bone mineral density. The biochemical parameters do not support the presence of hyperparathyroidism, renal disorders or other associated diseases influencing the bone mineral turnover. The evaluation of bone mineral density in the course of the preoperative planning is proposed in neurofibromatosis-1; the exact background and the role of a possible osteoporosis in the prognosis remain to be elucidated.

Increased chondrocyte death after steroid and local anesthetic combination

BackgroundHyaline articular cartilage has limited repair and regeneration capacity. Intraarticular administration of glucocorticoid and local anesthetic injections play an important role in the therapy of osteoarthritis. Glucocorticoids and anesthetics reportedly enhance apoptosis in chondrocytes, but effects of the combined use of glucocorticoids and local anesthetics are unknown.Questions/purposesWe asked whether glucocorticoid and local anesthetic agents combined had any synergistic effects on chondrocyte apoptosis.MethodsCell viability and apoptosis/necrosis assessment of human articular chondrocytes were performed in vitro (chondrocyte cell cultures) and ex vivo (osteochondral specimens) using flow cytometry and TUNEL analysis, respectively.ResultsGlucocorticoids and local anesthetics induce apoptosis in chondrocytes at various rates. When used in combination, the percentage of dead chondrocytes was increased in in vitro chondrocyte cell cultures and osteochondral ex vivo specimens.ConclusionsWe observed a time-dependent decrease in chondrocyte viability after concurrent steroid and local anesthetic exposure.Clinical RelevanceThe combination of glucocorticoids and local anesthetics has an adverse effect on articular chondrocytes, and it raises a question regarding whether concomitant administration should be used in treating osteoarthritis.

Breakthrough in three-dimensional scoliosis diagnosis: significance of horizontal plane view and vertebra vectors

Scoliosis is a multifactorial three-dimensional (3D) spinal deformity with integral and directly related vertebral deviations in the coronal, sagittal and horizontal planes. Current classification and diagnostic methods rely on two-dimensional (2D) frontal and lateral X-ray images; no routine methods are available for the visualization and quantitative evaluation of deviations in the horizontal plane. The EOS 2D/3D system presented here is a new, low-dose, orthopedic radiodiagnostic device based on Nobel prize-winning X-ray detection technology with special software for 3D surface reconstruction capabilities that finally led to a breakthrough in scoliosis diagnosis with high-quality, realistic 3D visualization and accurate quantitative parametric analysis. A new concept introducing vertebra vectors and vertebra vector parametric calculations is introduced that furnishes simplified visual and intelligible mathematical information facilitating interpretation of EOS 2D/3D data, especially with regard to the horizontal plane top view images. The concept is demonstrated by a reported scoliotic case that was readily characterized through information derived from vertebra vectors alone, supplemented with the current angulation measurement methods in the coronal and sagittal planes and axial vertebral rotation measurements in the horizontal plane, with a calibrated 3D coordinate system suitable for inter-individual comparisons. The new concept of vertebra vectors may serve as a basis for a truly 3D classification of scoliosis.

Frontometaphyseal dysplasia: mutations in FLNA and phenotypic diversity.

Frontometaphyseal dysplasia is an X‐linked trait primarily characterized by a skeletal dysplasia comprising hyperostosis of the skull and modeling anomalies of the tubular bones. Extraskeletal features include tracheobronchial, cardiac, and urological malformations. A proportion of individuals have missense mutations or small deletions in the X‐linked gene, FLNA. We report here our experience with comprehensive screening of the FLNA gene in a group of 23 unrelated probands (11 familial instances, 12 simplex cases; total affected individuals 32) with FMD. We found missense mutations leading to substitutions in the actin‐binding domain and within filamin repeats 9, 10, 14, 16, 22, and 23 of filamin A in 13/23 (57%) of individuals in this cohort. Some mutations present with a male phenotype that is characterized by a severe skeletal dysplasia, cardiac, and genitourinary malformations that leads to perinatal death. Although no phenotypic feature consistently discriminates between females with FMD who are heterozygous for FLNA mutations and those in whom no FLNA mutation can be identified, there is a difference in the degree of skewing of X‐inactivation between these two groups. This observation suggests that locus heterogeneity may exist for this disorder.

Geometrical values of the normal and arthritic hip and knee detected with the EOS imaging system

PurposeEOS 2D/3D is an integrated, low-dose orthopedic digital radioimaging solution, which, due to its groundbreaking properties, has recently shown an increasing application in scoliosis surgery. Its integrated sterEOS 3D software allows creation of patient-specific three-dimensional (3D) lower limb models, and can produce geometrical parameters in 3D. Currently there are a limited number of reports on EOS for lower limb applications.MethodsThree-dimensional reconstructions of 256 hip and knee joints of 128 healthy subjects, as well as 53 hips and 46 knees of 69 patients with hip or knee arthritis, were evaluated based on orthogonal EOS two-dimensional (2D) images. Measurements for hips included femur and tibia length, total length of the extremity, femoral antetorsion and offset, femoral neck length, neck-shaft and hip-knee-shaft (HKS) angles. Lower limb alignment in both frontal and sagittal planes were determined in normal and arthritic knees. Values were compared with those obtained by standard methods published by others.ResultsNormal hip and knee geometrical parameters were found in our healthy subjects. In osteoarthritic cases, values for neck-shaft angle, femoral antetorsion, femur length and total length of the extremity were shown to decrease non-significantly. Evaluation of lower limb alignment in healthy and arthritic knees showed normal values in healthy subjects apart from three cases with an average six degrees varus. Arthritic knees were most frequently found to have a varus angulation, with the exception of 11 cases with normal or valgus alignment.ConclusionEOS 2D/3D with its sterEOS 3D reconstruction is useful for a comprehensive 3D examination of the lower limb. In the near future it may be suitable for daily routine diagnostics of orthopedic lower limb deformities as a primary examination method.

Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis.

Study Design. A genetic association study was performed on 126 patients with adolescent idiopathic scoliosis and 197 healthy controls from independent Hungarian pedigrees. Objective. To reveal implication of promoter polymorphisms of bone morphogenetic protein 4 (BMP4), interleukin-6 (IL6), leptin, matrix metalloproteinase-3 (MMP3), melatonin 1B receptor (MTNR1B) genes in adolescent idiopathic scoliosis (AIS). Combinatorial association of these candidate genes was also studied to detect additive effect of certain single-nucleotide polymorphism (SNP) patterns. Summary of Background Data. It was previously unraveled that IL6, MMP3, and MTNR1B genes could be considered as predisposition genes of AIS. Since BMP4 and leptin play a central role in bone formation and remodeling and are in direct interaction with melatonin, IL6, and MMP3, these also can be potential predisposition genes. Methods. The genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism. Results. At a single gene level, no significant differences were found for allele and genotype frequencies of the polymorphisms of these genes between cases or controls; therefore, the formerly detected association of IL6, MMP3, and MTNR1B with AIS was not confirmed in the Hungarian population by independent SNP analysis. However, significantly increased AIS risk was observed at particular combinations of genotypes of paired SNPs of the candidate genes. Conclusions. The genetic effect of promoter polymorphisms of BMP4, IL6, leptin, MMP3, and MTNR1B can be synergistic for susceptibility to AIS. The combinatorial effect can modulate the final biological impact of many susceptibility polymorphisms; therefore, this should be considered at the comparison of results from case-control studies of different populations.

Prevalence of low back pain and lumbar spine degenerative disorders. Questionnaire survey and clinical–radiological analysis of a representative Hungarian population

A cross-sectional epidemiological study via personal interviews was performed regarding low back pain and its related clinical aspects in a Hungarian sample of 10,000 people. Joining the international campaign of the “Bone and Joint Decade”, our aim was to give data on low back pain prevalence and to explore the underlying possible clinical conditions in a Central European adult and adolescent population. Ten thousand people aged 14–65, selected randomly by the Hungarian central office of statistics from three counties of the south-western Hungarian region, were surveyed using a special questionnaire focusing on low back pain and other degenerative spinal symptoms. People with low back pain complaints and written consent were asked to participate in a further clinical investigation, where radiological and clinical assessment was performed. A total of 4,389 persons (44.1%) reported low back pain in the last month at the time of the survey. Work absenteeism due to low back pain affected 2,140 persons (21.5%). A total of 292 people (2.9%) had already undergone spinal surgery. Upon request 682 people came for a clinical follow-up, where thorough physical examination and radiological analysis was performed and results were statistically interpreted. The Oswestry disability index (ODI) in the examined group of patients averaged 35.1%; radiological degenerative signs were observed in 392/682 (57.5%). Individuals with signs of radiological degeneration had a statistically significant higher ODI value, age, and a higher, yet not significantly increased BMI value than radiographically negative patients (p < 0.05). Co-existence of hip and knee osteoarthritis was also investigated. Higher osteoarthritis prevalence was found in individuals with radiographic signs of spinal degeneration. Details of the survey and clinical investigations are discussed.

Comparison of scoliosis measurements based on three-dimensional vertebra vectors and conventional two-dimensional measurements: advantages in evaluation of prognosis and surgical results

PurposeA new concept of vertebra vectors based on spinal three-dimensional (3D) reconstructions of images from the EOS system, a new low-dose X-ray imaging device, was recently proposed to facilitate interpretation of EOS 3D data, especially with regard to horizontal plane images. This retrospective study was aimed at the evaluation of the spinal layout visualized by EOS 3D and vertebra vectors before and after surgical correction, the comparison of scoliotic spine measurement values based on 3D vertebra vectors with measurements using conventional two-dimensional (2D) methods, and an evaluation of horizontal plane vector parameters for their relationship with the magnitude of scoliotic deformity.Methods95 patients with adolescent idiopathic scoliosis operated according to the Cotrel-Dubousset principle were subjected to EOS X-ray examinations pre- and postoperatively, followed by 3D reconstructions and generation of vertebra vectors in a calibrated coordinate system to calculate vector coordinates and parameters, as published earlier. Differences in values of conventional 2D Cobb methods and methods based on vertebra vectors were evaluated by means comparison T test and relationship of corresponding parameters was analysed by bivariate correlation. Relationship of horizontal plane vector parameters with the magnitude of scoliotic deformities and results of surgical correction were analysed by Pearson correlation and linear regression.ResultsIn comparison to manual 2D methods, a very close relationship was detectable in vertebra vector-based curvature data for coronal curves (preop r 0.950, postop r 0.935) and thoracic kyphosis (preop r 0.893, postop r 0.896), while the found small difference in L1–L5 lordosis values (preop r 0.763, postop r 0.809) was shown to be strongly related to the magnitude of corresponding L5 wedge. The correlation analysis results revealed strong correlation between the magnitude of scoliosis and the lateral translation of apical vertebra in horizontal plane. The horizontal plane coordinates of the terminal and initial points of apical vertebra vectors represent this (r 0.701; r 0.667). Less strong correlation was detected in the axial rotation of apical vertebras and the magnitudes of the frontal curves (r 0.459).ConclusionsVertebra vectors provide a key opportunity to visualize spinal deformities in all three planes simultaneously. Measurement methods based on vertebral vectors proved to be just as accurate and reliable as conventional measurement methods for coronal and sagittal plane parameters. In addition, the horizontal plane display of the curves can be studied using the same vertebra vectors. Based on the vertebra vectors data, during the surgical treatment of spinal deformities, the diminution of the lateral translation of the vertebras seems to be more important in the results of the surgical correction than the correction of the axial rotation.

Prevalence of radiographic primary hip and knee osteoarthritis in a representative Central European population

The aim of our study was to determine the radiographic prevalence of hip and knee osteoarthritis and compare our results with prevalence data reported by other studies, as no similar study had been performed in Hungary previously. Our aim was also to investigate the usefulness of the different radiological scoring methods for the definition of osteoarthritis. Patients who earlier reported complaints and gave written consent were asked to participate in a clinical follow-up. In the 682 participants Harris hip score, visual analogue pain scale values for both joints, Knee Society score and knee functional score were calculated. Weight-bearing radiographs were taken of both joints. Kellgren-Lawrence radiological evaluation was performed and osteoarthritis prevalence was defined. Hip osteoarthritis was found in 109 cases (16.49%), and knee osteoarthritis was found in 111 cases (16.54%). Harris hip score, Knee Society score, functional score and visual analogue scale values were significantly worse in people with radiographically proven osteoarthritis compared to the control group (p < 0.05). Significantly higher osteoarthritis prevalence of both joints was found in those with increased body mass index values. Age also plays a significant role in the development of both hip and knee osteoarthritis. No significant difference was observed between male and female participants regarding osteoarthritis prevalence. The Kellgren-Lawrence score with a cut-off value of 2 or more is a useful evaluation method for the detection of osteoarthritis prevalence in epidemiological studies; according to our observations, in clinical practice a cut-off value of three or more is more relevant.

Prevalence of degenerative joint complaints of the lower extremity: a representative study

As part of the international campaign of the bone and joint decade, we aimed to present epidemiological data on the prevalence of major joint complaints in a Central European region. Ten thousand subjects aged between 14 and 65, selected randomly by the Hungarian central office of statistics from three counties in southern Hungary, were surveyed using our own questionnaire based on widely accepted scoring systems in the literature, focusing on major degenerative joint complaints, and using the short form 36 (SF-36) questionnaire. We found that the prevalence of hip pain in the observed group was 22.2%, the prevalence of knee pain 30.3%, and frequent ankle pain occurred in 9.7%. The results of the SF-36 questionnaire showed that with the exception of social function, neither of the values of the examined health dimensions reached levels of other international surveys. Details of the survey and the possible causes of the higher prevalence are discussed, along with the results of the SF-36 questionnaire.RésuméEn collaboration avec la campagne internationale sur la bone and joint decade, notre but a été de mettre en évidence des données épidémiologiques sur la prévalence des lésions articulaires, dans une région du centre Europe. Pour cela, 10.000 patients âgés entre 14 et 65 ans ont été sélectionnés par l’Office Cental Hongrois de Statistiques, patients provenant de trois comtés du Sud de la Hongrie en usant d’un questionnaire, rempli par les patients eux-mêmes et basé sur des scores largement acceptés par la population orthopédique et, notamment, le score SF 36. Nous avons trouvé une prédominance de douleur de la hanche dans ce groupe, avec un taux de 22,8%, le pourcentage de douleur du genou étant de 30,8% et, celle de la cheville, de 9,7%. Les résultats du questionnaire SF 36 ont montré qu’en dehors des problèmes sociaux, les valeurs retrouvées se situaient à des niveaux comparables à ceux d’autres études internationales. Les détails de cette étude et les étiologies possibles sont discutés avec les résultats du questionnaire SF 36.